FDA's Future Inspection Plans Need to Address Issues Presented by COVID-19 Backlog (GAO-21-409T)
Summary
GAO testimony, GAO-21-409T, before the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies of the House Committee on Appropriations, for release on March 4, 2021. It is the statement of Mary Denigan-Macauley, Director, Health Care, on drug safety. It states that fiscal year 2015 was the first time the Food and Drug Administration (FDA) conducted more inspections of foreign drug manufacturers than domestic manufacturers, with the majority conducted in China and India. Its title states that FDA's future inspection plans need to address issues presented by the COVID-19 inspection backlog.
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United States Government Accountability Office
Testimony before the Subcommittee on
Agriculture, Rural Development, Food
and Drug Administration, and Related
Agencies, Committee on Appropriations,
House of Representatives
DRUG SAFETY
For Release on Delivery
Expected at 10:00 a.m. EST
Thursday, March 4, 2021
FDA’s Future Inspection
Plans Need to Address
Issues Presented by
COVID-19 Backlog
Statement of Mary Denigan-Macauley, Director,
Health Care
GAO-21-409T
March 2021
DRUG SAFETY
FDA’s Future Inspection Plans Need to Address
Issues Presented by COVID-19 Backlog
Highlights of GAO-21-409T, a testimony
before the Subcommittee on Agriculture, Rural
Development, Food and Drug Administration,
and Related Agencies, Committee on
Appropriations, House of Representatives
Why GAO Did This Study What GAO Found
The outbreak of COVID-19 has called Fiscal year 2015 was the first time that the Food and Drug Administration (FDA)
greater attention to the United States’ conducted more inspections of foreign drug manufacturers than domestic
reliance on foreign drug manufacturers, with the majority conducted in China and India. However, in June
manufacturers. FDA reports that 74 2020, GAO reported that from fiscal year 2016 through fiscal year 2018, both
percent of establishments foreign and domestic inspections decreased, in part due to staffing vacancies.
manufacturing active ingredients and While foreign inspections increased in 2019, since March 2020, FDA has largely
54 percent of establishments paused foreign and domestic inspections due to the Coronavirus Disease 2019
manufacturing finished drugs for the (COVID-19) pandemic, conducting only those deemed mission critical. In
U.S. market were located overseas, as
January 2021, GAO reported that FDA conducted three foreign inspections in
of May 2020. FDA is responsible for
fiscal year 2020 following the pause—significantly less than in recent years.
overseeing the safety and
effectiveness of all drugs marketed in Number of FDA-Conducted Foreign Drug Manufacturing Establishment Inspections, Fiscal
the United States, regardless of where Years 2019–2020, by Month
they are produced, and it conducts
inspections of both foreign and
domestic manufacturing
establishments.
GAO has had long-standing concerns
about FDA's ability to oversee the
increasingly global pharmaceutical
supply chain, an issue highlighted in
GAO's High Risk Series since 2009.
This statement is largely based on FDA has used alternative inspection tools to maintain some oversight of drug
GAO’s Drug Manufacturing Inspections manufacturing quality while inspections are paused. These tools include relying
enclosure in its January 2021 CARES on inspections conducted by foreign regulators, requesting and reviewing records
Act report, as well as GAO’s December and other information, and sampling and testing drugs. FDA has determined that
2019 and June 2020 testimonies.
inspections conducted by certain European regulators are equivalent to and can
Specifically, it discusses (1) the
be substituted for an FDA inspection. Other tools provide useful information but
number of FDA’s foreign inspections,
(2) FDA’s response to the COVID-19 are not equivalent. In addition, FDA was unable to complete more than 1,000 of
pandemic pause in inspections, and (3) its planned fiscal year 2020 inspections and will likely face a backlog of
persistent foreign inspection inspections in future years. In January 2021, GAO recommended that FDA
challenges. For that work, GAO ensure that inspection plans for future fiscal years respond to the issues
examined FDA data from fiscal years presented by the backlog and that FDA fully assess the agency’s alternative
2012 through 2020, interviewed FDA inspection tools. FDA concurred with both recommendations.
investigators, and reviewed documents
Even before the COVID-19 pandemic, FDA faced persistent challenges
related to drug oversight during the
conducting foreign inspections. GAO found in December 2019 that there
COVID-19 pandemic, among other
things.
continued to be vacancies among the investigators who conduct foreign
inspections. GAO further found that FDA's practice of preannouncing foreign
inspections up to 12 weeks in advance could give manufacturers the opportunity
to fix problems ahead of the inspection and raised questions about their
equivalence to domestic inspections. In light of COVID-19, FDA is now
preannouncing both foreign and domestic inspections for the safety of its staff
and manufacturers. GAO also found that language barriers can create
View GAO-21-409T. For more information,
challenges during foreign inspections as FDA generally relies on the
contact Mary Denigan-Macauley at (202) 512- establishment for translation services.
7114 or deniganmacauleym@gao.gov.
United States Government Accountability Office
Letter Letter
Chairman Bishop, Ranking Member Fortenberry, and Members of the
Subcommittee:
I am pleased to be here today to discuss our work on the Food and Drug
Administration’s (FDA) oversight of drugs manufactured overseas. 1 The
outbreak of Coronavirus Disease 2019 (COVID-19) has called greater
attention to the United States’ reliance on foreign drug manufacturers and
highlighted once again the importance of ensuring a secure
pharmaceutical supply chain. Like the majority of other drugs
manufactured for the U.S. market, much of the manufacturing of drugs for
treating COVID-19 occurs overseas.
We have had long-standing concerns about FDA’s ability to oversee the
increasingly global pharmaceutical supply chain, an issue highlighted in
our High Risk Series since 2009. 2 A critical element in FDA’s oversight of
overseas manufacturing is its inspection of foreign manufacturing
establishments. The COVID-19 pandemic has further complicated FDA’s
foreign inspection activities. Citing concern for the safety of its
employees, FDA announced in March 2020 that it was postponing most
inspections of foreign manufacturing establishments. Only inspections
deemed mission critical would still be considered on a case-by-case
basis. In its announcement, FDA stated that it had other tools to ensure
the safety of the U.S. drug supply and that it was evaluating additional
ways to conduct its inspections.
My remarks today primarily discuss findings on FDA’s foreign drug
inspection program that we previously reported in December 2019 and
June 2020 testimonies, and in our Drug Manufacturing Inspections
1Drugs are defined to include, among other things, articles intended for use in the
diagnosis, cure, mitigation, treatment, or prevention of disease and include components of
those articles. See 21 U.S.C. § 321(g)(1)(B), (D). An active pharmaceutical ingredient
includes, among other things, any component that is intended to provide pharmacological
activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of
disease. See 21 C.F.R. § 207.1 (2019). In this testimony, we refer both to drug products—
drugs in their finished dosage forms—and to active pharmaceutical ingredients as “drugs.”
2See GAO, High-Risk Series: Substantial Efforts Needed to Achieve Greater Progress on
High-Risk Areas, GAO-19-157SP (Washington, D.C.: Mar. 6, 2019). See also GAO, Food
and Drug Administration: Improvements Needed in the Foreign Drug Inspection Program,
GAO/HEHS-98-21 (Washington, D.C.: Mar. 17, 1998) and Drug Safety: Better Data
Management and More Inspections Are Needed to Strengthen FDA’s Foreign Drug
Inspection Program, GAO-08-970 (Washington, D.C.: Sept. 22, 2008).
Page 1 GAO-21-409T
enclosure in the January 2021 CARES Act report. 3 Specifically, this
statement provides observations on
(1) the number of FDA’s foreign inspections,
(2) FDA’s response to the COVID-19 pandemic pause in inspections,
and
(3) persistent foreign inspection challenges.
For our prior work, we analyzed FDA data from fiscal year 2012 through
fiscal year 2020 on inspections of foreign drug manufacturing
establishments and interviewed FDA drug investigators. Further, we
reviewed agency documents, and interviewed FDA officials related to the
agency’s drug oversight activities during the COVID-19 pandemic. More
detailed information on our objectives, scope, and methodology for that
work can be found in the two testimonies and January 2021 report. 4 We
also obtained updates from FDA on the status of inspections, as of
February 2021, for this testimony statement. The work on which this
statement is based was conducted in accordance with generally accepted
government auditing standards. Those standards require that we plan
and perform the audit to obtain sufficient, appropriate evidence to provide
a reasonable basis for our findings and conclusions based on our audit
objectives. We believe that the evidence obtained provides a reasonable
basis for our findings and conclusions based on our audit objectives.
Drugs sold in the United States—including active pharmaceutical
Background ingredients and finished dosage forms—are manufactured throughout the
world. According to FDA, as of May 2020, 74 percent of establishments
manufacturing active pharmaceutical ingredients and 54 percent of
establishments manufacturing finished drugs for the U.S. market were
3See GAO, Drug Safety: Preliminary Findings Indicate Persistent Challenges with FDA
Foreign Inspections, GAO-20-262T (Washington, D.C.: Dec. 10, 2019); Drug Safety:
COVID-19 Complicates Already Challenged FDA Foreign Inspection Program,
GAO-20-626T (Washington, D.C.: June 2, 2020); and COVID-19: Critical Vaccine
Distribution, Supply Chain, Program Integrity, and Other Challenges Require Focused
Federal Attention, GAO-21-265 (Washington, D.C.: Jan. 28, 2021).
4GAO-20-262T, GAO-20-626T, and GAO-21-265.
Page 2 GAO-21-409T
located overseas. 5 As of March 2019, FDA data showed that India and
China had the most manufacturing establishments shipping drugs to the
United States, with about 40 percent of all foreign establishments in these
two countries. (See fig. 1.)
Figure 1: The 10 Countries with the Most Foreign Drug Establishments Shipping to the United States as of March 2019
Note: This figure includes the 10 countries with the most foreign drug establishments shipping to the
United States and does not include those countries with fewer than 70 establishments. The count of
foreign establishments represents the number of establishments that were known to ship or were
likely to ship a drug to the United States as of March 2019. This count excludes about 380
establishments that participate in some aspect of the manufacturing process, such as sterilizers and
analytical labs, but do not ship products to the United States directly. Such establishments are also
subject to inspection.
5Judith A. McMeekin, Pharm.D., Associate Commissioner for Regulatory Affairs, Office of
Regulatory Affairs, Mark Abdoo, Associate Commissioner for Global Policy and Strategy,
and Douglas Throckmorton, M.D., Deputy Director for Regulatory Programs, Center for
Drug Evaluation and Research, Food and Drug Administration, COVID-19 and Beyond:
Oversight of the FDA's Foreign Drug Manufacturing Inspection Process, testimony before
the Senate Committee on Finance, 116th Cong., 2nd sess., June 2, 2020. According to
FDA, although the agency has information on the location of drug manufacturing
establishments, it does not have information on the volume of drug ingredients these
establishments manufacture for the U.S. market.
Page 3 GAO-21-409T
FDA is responsible for overseeing the safety and effectiveness of all
drugs marketed in the United States, regardless of where they are
manufactured. Drugs manufactured overseas to be offered for import and
sale in the United States must meet the same statutory and regulatory
standards as those manufactured in this country. FDA’s Center for Drug
Evaluation and Research establishes standards for the safety, quality,
and effectiveness of, and manufacturing processes for, over-the-counter
and prescription drugs. FDA’s Office of Regulatory Affairs inspects both
domestic and foreign establishments to ensure that drugs are produced in
conformance with applicable laws of the United States, including current
good manufacturing practice (CGMP) regulations. 6
FDA typically conducts 1) preapproval inspections before approving a
new brand name or generic drug; 2) surveillance inspections periodically
based on a risk analysis after a drug is marketed to ensure continued
compliance with applicable laws and regulations; and 3) for-cause
inspections to investigate specific issues or follow-up on previous FDA
regulatory action. To prioritize establishments for surveillance inspections,
FDA applies a risk-based site selection model to its catalog of
establishments to identify those establishments (both domestic and
foreign) that, based on the characteristics of the drugs being
manufactured, pose the greatest potential public health risk should they
experience a manufacturing defect. Through this process, FDA develops
a ranked list of establishments for inspection.
In 1998, and again in 2008, we found that FDA inspected relatively few
foreign drug manufacturing establishments and that challenges unique to
foreign inspections influenced the manner in which FDA conducted such
inspections. 7 In our 2008 report we recommended that FDA increase the
number of foreign inspections it conducts, and FDA agreed with our
recommendation. We found in 2010, and again in 2016, that FDA was
conducting more inspections of foreign establishments. 8 In our 2008
6CGMPs provide for systems that assure proper design, monitoring, and control of
manufacturing processes and facilities. See 21 C.F.R. pts. 210, 211, 212 (2019). FDA
considers nearly all drug establishment inspections to include an assessment of CGMPs.
7GAO/HEHS-98-21 and GAO-08-970.
8See GAO, Drug Safety: FDA Has Conducted More Foreign Inspections and Begun to
Improve Its Information on Foreign Establishments, but More Progress Is Needed,
GAO-10-961 (Washington, D.C.: Sept. 30, 2010) and Drug Safety: FDA Has Improved Its
Foreign Drug Inspection Program, but Needs to Assess the Effectiveness and Staffing of
Its Foreign Offices, GAO-17-143 (Washington, D.C.: Dec. 16, 2016).
Page 4 GAO-21-409T
report we also found that, because of inaccurate information in FDA’s
databases, the agency did not know how many foreign drug
establishments were subject to inspection. 9 We recommended that FDA
take steps to improve the accuracy of this registration information. In our
2010 and 2016 reports we found that FDA had taken steps to improve the
accuracy and completeness of information in its catalog of drug
establishments subject to inspection, such as using contractors to
conduct site visits to verify the existence of registered foreign
establishments and confirm that they manufacture the products that are
recorded in U.S. import records.
FDA’s Foreign
Inspections Declined
in Recent Years After
Several Years of
Increases, and Then
Mostly Stopped Due
to the COVID-19
Pandemic
Prior to the COVID-19 As we reported in our June 2020 testimony, the number of FDA foreign
Pandemic, FDA Foreign drug manufacturing establishment inspections increased from fiscal year
2012 through fiscal year 2016, surpassing the number of domestic
Drug Inspections Had inspections for the first time. 10 However, we found that from fiscal year
Increased for Several 2016 through 2018, both foreign and domestic inspections decreased—
Years, but Started by about 10 percent and 13 percent, respectively. FDA officials attributed
Trending Downward in the decrease to vacancies in the number of investigators available to
Fiscal Year 2017 conduct inspections (which we discuss later in this testimony statement)
and to inaccurate data used to select establishments for inspection in
9GAO-08-970.
10GAO-20-626T.
Page 5 GAO-21-409T
fiscal years 2017 and 2018. 11 FDA conducted more foreign inspections in
fiscal year 2019 than in fiscal year 2018, but the total number of
inspections continued to decline from the fiscal year 2016 peak.
In addition, we found that FDA continued to conduct the largest number of
foreign inspections in India and China, with almost half of fiscal year 2019
foreign inspections conducted in these two countries. (See table 1.) In
addition to India and China, the rest of the countries in which FDA most
frequently conducted inspections has generally been the same since our
2008 report. 12
Table 1: Total Number of FDA Foreign Drug Inspections, by Country, Fiscal Years 2012 through 2019
Country 2012 2013 2014 2015 2016 2017 2018 2019
India 140 110 114 204 207 219 252 305
China 59 74 113 127 173 165 153 167
Canada 49 51 39 52 56 72 48 70
Germany 59 60 72 68 72 69 68 69
Japan 49 28 47 31 65 46 43 51
All other countries 269 314 394 358 462 422 371 315
Total foreign 625 637 779 840 1,035 993 935 977
Total domestic 1,184 1,030 897 784 882 772 742 694
Total inspections 1,809 1,667 1,676 1,624 1,917 1,765 1,677 1,671
Source: GAO analysis of Food and Drug Administration (FDA) data. | GAO-21-409T
Note: The total number of inspections includes those conducted for preapproval, surveillance, and
for-cause purposes.
11We reported in December 2019 that an FDA effort to inspect approximately 1,000
foreign establishments that lacked an inspection history contributed to the decline in the
number of foreign inspections because a sizeable percentage of these establishments
were not actually subject to inspection. Therefore, these establishments were removed
from the inspection list. FDA officials told us that domestic establishments replaced these
removed establishments as they were the next highest priority establishments identified
through the model.
12GAO-08-970.
Page 6 GAO-21-409T
FDA Postponed Most In our January 2021 report, we found that the total number of FDA
Foreign Inspections since inspections of foreign establishments was about 60 percent lower in fiscal
year 2020 than during each of the previous 2 fiscal years. 13 From March
March 2020 Due to the
2020 (when FDA announced it would temporarily not conduct any foreign
COVID-19 Pandemic or domestic inspections other than those deemed mission critical) through
the end of the fiscal year, FDA conducted three foreign mission critical
inspections—one each in Canada, Germany, and India. In contrast,
during the same time frame in each of the prior 2 years, FDA conducted
more than 600 foreign inspections. FDA’s domestic inspection activities
also decreased significantly in 2020, though FDA conducted more
domestic inspections than foreign inspections during the pandemic—52
from March through October 1, 2020. 14 (See fig. 2.)
13GAO-21-265.
14In July 2020, FDA announced that it planned to resume domestic inspections,
contingent on a rating system that incorporates information on COVID-19 infection trends
in a geographic area. Depending on an area’s rating, FDA’s inspection activities were to
range from mission critical inspections only to the resumption of all inspections. According
to FDA’s area rating data, as of December 3, 2020, conditions were appropriate for
conducting routine surveillance inspections in 49 U.S. counties, with regulatory activity
limited to mission critical inspections only in the more than 3,000 remaining counties.
Page 7 GAO-21-409T
Figure 2: Domestic and Foreign Drug Manufacturing Establishment Inspections Conducted by FDA, Fiscal Years 2018-2020,
by Month
Page 8 GAO-21-409T
As of February 2021, FDA had begun conducting some foreign
inspections, but had not set a date for resuming routine foreign
surveillance inspections in all countries. FDA said it continues to monitor
the global situation and remains in contact with foreign regulators in
individual countries to inform FDA’s assessment of the feasibility of
resuming foreign surveillance inspections as conditions improve. FDA
reported that, in October 2020, staff in the agency’s China office had
begun conducting inspections in China. According to FDA, between
October 26, 2020, and January 14, 2021, these staff had conducted nine
preapproval inspections, but no surveillance inspections. FDA officials
told us that staff in the agency’s India office began conducting inspections
in India in January 2021 and had conducted two inspections as of
February 25, 2021.
COVID-19 Pandemic
Has Forced FDA to
Rely on Alternatives
to Inspections and the
Agency Will Likely
Face an Inspection
Backlog in the Future
FDA Has Relied on In January 2021, we reported that FDA used alternative tools to oversee
Alternative Tools in Lieu of drug manufacturing quality while inspections have been paused, including
the use of inspections conducted by foreign regulators, requesting and
Inspections During the
reviewing records and other information, and sampling and testing
Pandemic, but They Are drugs. 15 These tools provide useful information, but are not all considered
Not a Comprehensive or equivalent to an inspection conducted by FDA.
Long-Term Substitute
Inspections conducted by some foreign regulators, when available,
can substitute for FDA inspections. In light of the COVID-19 pause in
inspections, FDA expanded the use of the mutual recognition agreement
it has with the European Union to include inspections conducted outside
of Europe by European regulators as a full substitute for FDA
15GAO-21-265.
Page 9 GAO-21-409T
inspections. 16 However, this only applies to certain European regulators
whose inspections FDA has found to be equivalent to its own. 17
Inspections from other select countries (such as Australia and Japan) can
be used for oversight purposes, but are not considered by FDA as
substitutes for an FDA inspection.
FDA can request and review records and other information to
substitute for FDA preapproval inspections in certain
circumstances. During the COVID-19 pandemic, FDA substantially
increased use of its authority to request that establishments provide
records in advance of or in lieu of an inspection, requesting records from
establishments in China, India, and the United States, among others. 18 In
certain cases, FDA can substitute the review of records and other
information for conducting a preapproval inspection, but such information
alone cannot be used as a substitute for an FDA surveillance inspection.
Sampling and testing are not a substitute for an inspection. In
response to the COVID-19 pandemic, FDA has adjusted the tool it uses
to automatically screen drug imports to help FDA determine where to
focus its sampling at the U.S. border, according to FDA officials.
However, sampling and testing alone do not specifically confirm
adherence to quality standards and thus cannot fully replace an FDA
inspection.
Alternative tools allowed FDA to take some regulatory action against
foreign drug manufacturing establishments with manufacturing
deficiencies during the inspection pause. From March 1, 2020, to
December 1, 2020, FDA placed 64 foreign establishments on import alert
for the following reasons:
• one based on issues identified in a foreign regulator inspection report;
16For the purposes of this report, when we refer to European regulators, we are referring
to the 27 European regulators that are part of the mutual recognition agreement with FDA,
plus the United Kingdom, which has a separate mutual recognition agreement.
17Inspections conducted outside of Europe by 19 of these 28 regulators can be
substituted for an FDA inspection as of January 2021.
18See 21 U.S.C. § 374(a)(4). Prior to the COVID-19 pandemic, FDA used this authority in
a more limited capacity to oversee 10 establishments that the agency would not routinely
inspect because of travel warnings. In fiscal year 2019, for example, this included
establishments in Colombia, Egypt, Israel, Mexico, Pakistan, and Saudi Arabia, among
others.
Page 10 GAO-21-409T
• nine for refusing FDA records requests or for deficiencies identified
during the agency’s review of records provided in response to an FDA
records request; and
• 54 based on issues identified from sampling. In addition, in January,
2021, FDA placed all alcohol-based hand sanitizers from Mexico on
import alert because it identified a high proportion of methanol
contamination in these drug products. 19
FDA May Face an As a result of the pause in inspections during the COVID-19 pandemic,
Inspection Backlog and FDA was unable to complete more than 1,000 of its planned fiscal year
2020 surveillance inspections. In selecting establishments for surveillance
Drug Approval Challenges
inspection each year, FDA prioritizes, as mandatory, those
as a Result of the Pause establishments never inspected or not inspected within 5 years.
in Inspections According to FDA officials, such establishments represent significant risks
to drug quality, but the extent of these risks is uncertain.
In order to achieve the agency’s strategic goal of risk-driven surveillance
inspections, with any resources remaining after mandatory inspections,
FDA seeks to maximize the number of inspections of establishments
prioritized by its risk-based site selection model each year. However, due
to the ongoing COVID-19 pandemic, domestic inspections continue to be
limited and the vast majority of foreign inspections continue to be
postponed, as of February 2021. If inspections continue to be postponed,
the backlog of mandatory inspections this will create could both extend
the maximum interval between inspections beyond FDA’s 5-year policy
and reduce the resources available in fiscal year 2022 for inspecting the
other highest priority establishments identified by its model (see fig. 3).
19Food and Drug Administration, FDA Takes Action to Place All Alcohol-Based Hand
Sanitizers from Mexico on Import Alert to Help Prevent Entry of Violative and Potentially
Dangerous Products into U.S., Protect U.S. Consumers, accessed February 22,
2021, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-
update-fda-takes-action-place-all-alcohol-based-hand-sanitizers-mexico-import.
Page 11 GAO-21-409T
Figure 3: Potential Effect of COVID-19 Backlog on Distribution of FDA’s Risk-Based Surveillance Inspections over Time if
Fiscal Year 2021 Inspections Continue to be Postponed
Note: Fiscal year 2020 and fiscal year 2021 percentages are based on the list of establishments
prioritized for inspection, which is issued in July of each year for the following fiscal year. Fiscal year
2022 percentages are our estimates based on the following assumptions: (1) that FDA will not
conduct any inspections of the establishments it has never inspected or for which the inspection is
outdated in fiscal year 2021 and so all of those inspections will roll over to fiscal year 2022; (2) that
there will be additional establishments that have never been inspected or for which the FDA
inspection is outdated (based on the average number of never and outdated inspections FDA
identified as mandatory in the last 2 years); and (3) FDA’s inspection capacity of 1,500 surveillance
inspections per year will not change. If FDA is able to resume surveillance inspections in fiscal year
2021 or use alternative tools as substitutes for FDA inspections, then it may be able to complete a
larger number of inspections of establishments, including those that have never been inspected, that
have not been inspected in 5 years, or those that are the highest risk remaining sites than is reflected
in our estimates and this figure.
Therefore, in January 2021, we recommended that FDA, as inspection
plans for future fiscal years are developed, ensure that such plans
identify, analyze, and respond to the issues presented by the backlog of
inspections that could jeopardize the goal of risk-driven inspections. 20
FDA concurred with the recommendation and stated that it was actively
tracking the list of sites that need to be inspected, and noted that the size
20GAO-21-265.
Page 12 GAO-21-409T
of the backlog will depend on the extent to which alternative inspection
tools are used.
The need to conduct preapproval inspections represents another
challenge for FDA. As of November 2020, FDA officials told us that the
agency had not experienced a significant effect on approval decisions
due to the COVID-19 inspection pause. FDA notes that it is continuing its
work to review and approve drug applications and that, as of October
2020, the agency had approved more than 600 brand name and generic
drug applications in 2020. Representatives from three associations
representing drug manufacturers stated that, because preapproval
inspections may happen months before an application is approved, the
postponement of inspections has not had a significant effect on FDA’s
ability to make drug approval decisions yet. However, two of these
associations noted that the longer inspections are postponed, the more
likely the inability to conduct a preapproval inspection could create larger
challenges for FDA’s ability to make approval decisions. FDA officials
said that they are expanding the use of alternative tools to mitigate the
effect of the pandemic on the agency’s ability to make approval decisions
when inspections are not possible.
FDA Has Not Fully In January 2021 we reported that, with the exception of European
Assessed How Its regulator inspection reports, FDA has not yet fully assessed how its
alternative tools can be used to supplement its regular inspection
Alternative Tools or Others
activities, or help meet its drug oversight objectives when inspections are
Can Be Used to Support not possible in the future. 21 We also noted that there may be additional
Its Current and Future tools for the agency to utilize when inspections are not possible.
Drug Oversight Activities According to FDA officials, the agency is in the process of assessing the
potential use, including its authority to use, other tools to serve as
supplements to FDA inspections. These include using remote video and
other remote and live interactions with establishment staff and records to
evaluate drug manufacturing operations.
We recommended that FDA fully assess its alternative inspection tools
and consider whether these tools or others could provide the information
needed to supplement regular inspection activities or help meet its drug
oversight objectives when inspections are not possible in the future. FDA
concurred with the recommendation and stated that it would continue to
evaluate these alternative tools and that the resulting information will help
it determine how such tools can be used to streamline and supplement
21GAO-21-265.
Page 13 GAO-21-409T
regular inspection activities and to prioritize inspections when normal
inspection operations are not possible. FDA stated that as it pursues
continued process improvements, the agency will incorporate this
recommendation in its ongoing assessment of these alternative
inspection tools.
Prior to COVID-19, FDA faced challenges to conducting its foreign
FDA Faced Persistent inspections. Many of these challenges—including inspection staff
Challenges to vacancies, preannouncing inspections, and translation barriers—are
longstanding issues and have been discussed in detail in our prior
Conducting Foreign reports.
Inspections Prior to
Foreign inspection staff vacancies. In December 2019, we found that
the COVID-19 FDA faced challenges filling staff vacancies in its foreign inspection
Pandemic workforce, and FDA officials said these vacancies contributed to the
decline in inspections. 22 At that time, FDA officials told us that the agency
was trying to fill its vacancies. However, officials have also told us that
new investigators are not typically used for foreign inspections until they
have been with the agency for 2 to 3 years. In June 2020, FDA testified
that it intended to fill all investigator vacancies in 2020, but as of
December 2020, investigator vacancies remained. 23 We plan to review
this issue as part of our ongoing examination of FDA’s foreign drug
inspection program.
Preannouncing inspections. In December 2019, we found that, prior to
COVID-19, there were differences in the amount of notice FDA generally
gives to foreign and domestic establishments because of challenges
inherent in conducting foreign inspections, and that this raises concerns
regarding their equivalence to domestic inspections. 24 Prior to COVID-19,
almost all domestic inspections were unannounced, whereas foreign
inspections were generally preannounced, which may give
establishments the opportunity to fix problems before the investigator
arrives. FDA testified in June 2020 that the agency usually announces
foreign surveillance inspections in advance, partly due to logistics such as
planning travel, arranging access to facilities, and securing visas, and
22GAO-20-262T.
23McMeekin, Abdoo, and Throckmorton, COVID-19 and Beyond.
24GAO-20-262T.
Page 14 GAO-21-409T
partly to avoid problems given the high costs of conducting foreign
inspections. 25
In our June 2020 testimony, we reported that FDA does conduct some
unannounced foreign inspections, particularly if the investigators
conducting the inspection are based in FDA’s foreign offices. 26 FDA
officials told us that the agency does not have data on the frequency with
which foreign drug inspections are unannounced, nor the extent to which
the amount of notice provided to foreign establishments varies. According
to FDA officials, this is because FDA does not have a data field in its
database to systematically track this information. 27 However, the officials
estimated that the agency generally gives 12 weeks of notice to
establishments that investigators are coming when investigators are
traveling from the United States. While investigators in FDA’s China and
India offices do conduct unannounced or short-notice inspections, these
staff do not perform most of the inspections in these countries. (See
table 2.)
25McMeekin, Abdoo, and Throckmorton, COVID-19 and Beyond.
26GAO-20-626T.
27In June 2020, we reported that FDA planned to add a new variable to its data to identify
preannounced and unannounced inspections, according to FDA officials.
Page 15 GAO-21-409T
Table 2: FDA Estimates of the Amount of Notice It Provides to Foreign Drug Establishments Prior to Inspection, by
Investigator Type, and the Percentage of Inspections in Which These Investigator Types Are Involved, Fiscal Year 2018
Percentage of inspections
involving this investigator
Type of investigator Amount of notice provided type in fiscal year 2018a
China office investigator Announcement: 0-5 days Involved in 27 percent of total number
FDA officials stated that investigators based in FDA’s China office of inspections in China
will announce surveillance inspections (those related to drugs
already on the U.S. market) to drug establishments 5 business
days in advance of an inspection. According to FDA officials, for-
cause inspections (those conducted in response to specific issues
or concerns) conducted by investigators based in the China office
are unannounced, meaning that they are not announced to the
drug establishments in advance.
India office investigator Announcement: 0-5 days Involved in 10 percent of total number
FDA officials stated that investigators based in FDA’s India office of inspections in India
will announce inspections to drug establishments 3 to 5 days in
advance of an inspection and can conduct short-notice
inspections that are announced 30 minutes before the inspection.
U.S.-based investigator Announcement: generally 12 weeks Involved in:
(Including dedicated FDA officials said that the agency generally announces foreign • 73 percent of total number of
foreign drug cadre) inspections conducted by domestically based investigators about inspections in China
12 weeks in advance. • 90 percent of total number of
inspections in India
• 100 percent of total number of
inspections in other foreign
countries
Source: Interviews with Food and Drug Administration (FDA) officials and GAO analysis of FDA data. | GAO-21-409T
a
These percentages add up to over 100 percent as some inspections may involve more than one type
of investigator.
In our January 2021 report we noted that of FDA’s fiscal year 2021
appropriation, $3.5 million is to be used for foreign unannounced drug
inspection pilots. 28 In February 2021, officials told us that FDA is
developing plans to implement a pilot. However, they said that in light of
the pandemic, FDA was preannouncing all domestic and foreign
28According to the Joint Explanatory Statement accompanying the Consolidated
Appropriations Act, 2021, $3.5 million of FDA’s fiscal year 2021 appropriation is to be
used for foreign unannounced human drug inspection pilots. See Explanatory Statement,
166 Cong. Rec. H7891 (daily ed. Dec. 21, 2020) (statement of Rep. Lowey); Pub. L. No.
16-260, § 4, 134 Stat. 1182, 1185 (2020) (clarifying that the explanatory statement
regarding this act shall have the same effect as a joint explanatory statement with respect
to the allocation of funds and implementation of certain divisions).
Page 16 GAO-21-409T
inspections for the foreseeable future to help assure the safety of
inspection staff and establishment employees.
Language barriers. In December 2019 we found that language barriers
continue to be a challenge to conducting foreign inspections. 29 Foreign
investigators generally rely on the drug establishment to provide
translation services, when needed. These services might be provided by
an English-speaking employee of the establishment being inspected, or
an external translator hired by the establishment. Investigators said that
there can be uncertainties regarding the accuracy of the information being
translated, particularly when investigators rely on the translation provided
by an employee of the establishment being inspected. It can also take
longer to complete typical inspection-related activities if the investigator
needs to rely on translation services. In January 2021 we found that FDA
also relies on drug establishments to translate the records and other
information that FDA has the authority to request in advance of or in lieu
of an inspection, an authority FDA has increased its use of during the
COVID-19 pandemic. 30 According to FDA policy, if translated, the
manufacturer should provide verification that the translation of the records
is complete and accurate, and copies of the original records should also
be included. Nevertheless, language barriers continue to present risks for
FDA—an area we plan to review as part of our ongoing examination of
FDA’s foreign drug inspection program.
We also reported in our December 2019 testimony that the overseas
travel schedule can present challenges for FDA’s domestically based
investigators, who conduct the majority of foreign inspections. For
example, there is little flexibility for domestically based investigators to
extend a foreign inspection because their inspections are scheduled
back-to-back in 3-week trips—extending one inspection would limit the
time on other scheduled inspections. Domestically based investigators
also faced challenges meeting post-inspection reporting requirements,
especially if serious deficiencies are identified during the inspection. 31
In conclusion, foreign manufacturing establishments continue to be a
critical source of drugs for millions of Americans, and FDA inspections are
a key tool to ensure the quality of these drugs. Over the years since we
29GAO-20-262T. We previously reported language barriers as a challenge to conducting
foreign inspections in our 2008 report (GAO-08-970).
30GAO-21-265.
31GAO-20-262T.
Page 17 GAO-21-409T
first examined this issue, FDA has made significant changes to adapt to
the globalization of the pharmaceutical supply chain and has greatly
increased the number of inspections it conducts of foreign
establishments. However, we found in December 2019 that the agency
faced many of the same challenges overseeing foreign establishments
that we identified over the last two decades. Subsequently, the outbreak
of COVID-19 has added a layer of complexity. Therefore, it will be
important for FDA to utilize lessons that it has learned during the COVID-
19 pandemic to improve its foreign drug inspection program, including
efforts to identify alternative mechanisms to satisfy foreign inspection
requirements and plans to address its growing backlog of inspections.
Chairman Bishop, Ranking Member Fortenberry, and Members of the
Subcommittee, this completes my prepared statement. I would be
pleased to respond to any questions that you may have at this time.
If you or your staff have any questions about this testimony, please
GAO Contact and contact Mary Denigan-Macauley, Director, Health Care at (202) 512-7114
Staff or DeniganMacauleyM@gao.gov. Contact points for our Offices of
Congressional Relations and Public Affairs may be found on the last page
Acknowledgments of this statement. GAO staff who made key contributions to this testimony
are William Hadley (Assistant Director); Katherine L. Amoroso (Analyst-in-
Charge); George Bogart; Zhi Boon; Kaitlin Farquharson; Cathleen
Hamann; Derry Henrick; John Lalomio; Laurie Pachter; Vikki Porter; and
Dan Ries.
(105028)
Page 18 GAO-21-409T
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